In recent years, bronchodilators (a β-agonist, a muscarinic antagonist, and the like) have been used for treatment of chronic obstructive pulmonary disease (COPD: chronic obstructive pulmonary disease, hereinafter may be referred to as “COPD”) and these are reported to improve airflow limitation temporarily (Non-Patent Literature 1).
Furthermore, ipratropium bromide, which is a muscarinic antagonist, is reported to exhibit a bronchodilator effect by relaxing bronchial smooth muscle (Non-Patent Literature 2).
Chronic obstructive pulmonary disease (COPD) is a disease in which various factors, particularly smoking causes chronic lung inflammation and the inflammation causes alveolar destruction and bronchial mucous gland hypertrophy, which in turn lead to shortness of breath and increased coughing or expectoration.
A disease previously referred to as pulmonary emphysema (PE) and a disease previously referred to as chronic bronchitis (CB) are often combined in various ratios and developed, and accordingly, the diseases caused by these two diseases came to be collectively referred to as chronic obstructive pulmonary disease (COPD).
According to a trial calculation made by the World Health Organization (WHO), three million people died of COPD worldwide in one year in 2005 and COPD is the fourth leading cause of death, and it is predicted that the number of deaths from COPD will increase further by 30% in the next 10 years. According to statistics by the Ministry of Health, Labor and Welfare in Japan, in 2005, deaths from COPD accounted for 1.3% of the total number of Japanese deaths and COPD is the tenth leading cause of death and the seventh leading cause of death exclusively in men.
The primary cause of COPD development is smoking. 90% of COPD patients are smokers (Non-Patent Literature 3) and the risk of smokers developing COPD is six or more times higher than that by nonsmokers. Approximately 10 to 15% of smokers develop COPD and, exclusively in the elderly population, nearly 50% of smokers suffer from COPD. Other causes include indoor air pollution or air pollution, inhalation of chemical substances or dust, genetic factors, pneumonia or bronchitis in childhood, and the like.
COPD is a disease whose characteristic condition is airflow limitation, that is, difficulty in breathing out, although the true nature of the condition is chronic airway inflammation. Smoking, inhaled substances, and the like cause inflammation in various sites in a lung ranging from a central airway to a peripheral bronchus. It is believed that the inflammation leads to protease-antiprotease imbalance, oxidant-antioxidant imbalance, and the like, which in turn causes alveolar destruction and bronchial mucous gland hypertrophy.
COPD is an incurable disease since irreversible destruction of the airway has occurred. Smoking cessation, pharmacotherapy by administration of e.g., a bronchodilator, an expectorant, and an antitussive drug, oxygen therapy, or the like can only relieve symptoms of COPD, and thus COPD is a very troublesome disease.
From the above-mentioned point of view, various kinds of agents for ameliorating COPD or methods for ameliorating COPD have been proposed so far (for example, Patent Literatures 1 and 2); however, development of an even better agent for ameliorating COPD is currently awaited.
In the above-mentioned context, the present inventors have worked toward development of an agent for ameliorating COPD by performing a study to search existing commercially available drugs. As a result, the present inventors have confirmed that mepenzolate bromide, which has been used as a therapeutic drug for irritable bowel, exhibited a therapeutic effect on COPD based on a bronchodilator effect and an anti-inflammatory effect thereof, and thus accomplished the present invention.
Mepenzolate bromide is known as an anticholinergic drug that has an effect of suppressing movement and contraction in a lower gastrointestinal tract and has been used as a therapeutic drug for irritable bowel in a clinical setting since 1967. However, it is unknown that mepenzolate bromide is effective for COPD treatment.
Furthermore, there has been no known therapeutic agent for COPD that has both a bronchodilator effect and an anti-inflammatory effect so far.